Heli Siljander1, Eeva Jason2, Terhi Ruohtula3, Jenni Selvenius4, Katariina Koivusaari5, Marja Salonen6, Suvi Ahonen7, Jarno Honkanen3, Jorma Ilonen8, Outi Vaarala9, Suvi M Virtanen7, Marja-Leena Lähdeaho10, Mikael Knip11. 1. Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. 2. Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland. 3. Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Clinicum, University of Helsinki, Helsinki, Finland. 4. Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland. 5. Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Food and Nutrition, University of Helsinki, Helsinki, Finland. 6. Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. 7. Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; Tampere University Hospital, Research, Development and Innovation Center, Tampere, Finland; Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland. 8. Immunogenetics Laboratory, University of Turku and Turku University of Hospital, Turku, Finland. 9. Clinicum, University of Helsinki, Helsinki, Finland. 10. Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland; Department of Pediatrics, Tampere University Hospital, Tampere, Finland. 11. Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland; Department of Pediatrics, Tampere University Hospital, Tampere, Finland. Electronic address: mikael.knip@helsinki.fi.
Abstract
OBJECTIVES: To assess whether weaning to an extensively hydrolyzed formula (EHF) decreases gut permeability and/or markers of intestinal inflammation in infants with HLA-conferred diabetes susceptibility, when compared with conventional formula. STUDY DESIGN: By analyzing 1468 expecting biological parent pairs for HLA-conferred susceptibility for type 1 diabetes, 465 couples (32 %) potentially eligible for the study were identified. After further parental consent, 332 babies to be born were randomized at 35th gestational week. HLA genotyping was performed at birth in 309 infants. Out of 87 eligible children, 73 infants participated in the intervention study: 33 in the EHF group and 40 in the control group. Clinical visits took place at 3, 6, 9, and 12 months of age. The infants were provided either EHF or conventional formula whenever breastfeeding was not available or additional feeding was required over the first 9 months of life. The main outcome was the lactulose to mannitol ratio (L/M ratio) at 9 months. The secondary outcomes were L/M ratio at 3, 6, and 12 months of age, and fecal calprotectin and human beta-defensin 2 (HBD-2) levels at each visit. RESULTS: Compared with controls, the median L/M ratio was lower in the EHF group at 9 months (.006 vs .028; P = .005). Otherwise, the levels of intestinal permeability, fecal calprotectin, and HBD-2 were comparable between the two groups, although slight differences in the age-related dynamics of these markers were observed. CONCLUSIONS: It is possible to decrease intestinal permeability in infancy through weaning to an extensively hydrolyzed formula. This may reduce the early exposure to dietary antigens. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01735123.
OBJECTIVES: To assess whether weaning to an extensively hydrolyzed formula (EHF) decreases gut permeability and/or markers of intestinal inflammation in infants with HLA-conferred diabetes susceptibility, when compared with conventional formula. STUDY DESIGN: By analyzing 1468 expecting biological parent pairs for HLA-conferred susceptibility for type 1 diabetes, 465 couples (32 %) potentially eligible for the study were identified. After further parental consent, 332 babies to be born were randomized at 35th gestational week. HLA genotyping was performed at birth in 309 infants. Out of 87 eligible children, 73 infants participated in the intervention study: 33 in the EHF group and 40 in the control group. Clinical visits took place at 3, 6, 9, and 12 months of age. The infants were provided either EHF or conventional formula whenever breastfeeding was not available or additional feeding was required over the first 9 months of life. The main outcome was the lactulose to mannitol ratio (L/M ratio) at 9 months. The secondary outcomes were L/M ratio at 3, 6, and 12 months of age, and fecal calprotectin and human beta-defensin 2 (HBD-2) levels at each visit. RESULTS: Compared with controls, the median L/M ratio was lower in the EHF group at 9 months (.006 vs .028; P = .005). Otherwise, the levels of intestinal permeability, fecal calprotectin, and HBD-2 were comparable between the two groups, although slight differences in the age-related dynamics of these markers were observed. CONCLUSIONS: It is possible to decrease intestinal permeability in infancy through weaning to an extensively hydrolyzed formula. This may reduce the early exposure to dietary antigens. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01735123.
Authors: Santosh Lamichhane; Heli Siljander; Marja Salonen; Terhi Ruohtula; Suvi M Virtanen; Jorma Ilonen; Tuulia Hyötyläinen; Mikael Knip; Matej Orešič Journal: Front Nutr Date: 2022-05-24
Authors: Petra M Pöllänen; Taina Härkönen; Jorma Ilonen; Jorma Toppari; Riitta Veijola; Heli Siljander; Mikael Knip Journal: J Clin Endocrinol Metab Date: 2022-02-17 Impact factor: 5.958